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Conserved role for G protein β5 /R7 complexes in the regulation of reactive oxygen species and defense of neurons against oxidative stress
Author(s) -
Simonds William F,
Zhang JianHua,
Jacob Leelamma Panicker,
Min KyungTai
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a917-d
Subject(s) - reactive oxygen species , oxidative stress , sod1 , microbiology and biotechnology , biology , nadph oxidase , superoxide dismutase , transfection , gene isoform , gq alpha subunit , transgene , signal transduction , g protein , biochemistry , gene
G protein β 5 is a neuronally‐expressed Gβ isoform that complexes with regulator of G protein signaling (RGS) proteins of the R7 subfamily and is highly evolutionarily conserved. Gene knockout studies of Gβ 5 have thus far revealed only limited phenotypes such as delayed egg‐laying in C. elegans , and defective visual adaptation in mice where the retinal variant of Gβ 5 functions in the deactivation of phototransduction. Consequently, the physiological significance of Gβ 5 in the brain and nervous system is not well understood. By overexpression of Gβ 5 in Drosophila neurons and rat PC12 cells we demonstrate that Gβ 5 induces antioxidant activity and enhances resistance to oxidative stress. Transgenic overexpression of Gβ 5 in Drosophila neurons extends the lifespan of flies. In both Gβ 5‐overexpressing flies and PC12 cells these effects are associated with reduced reactive oxygen species (ROS) and elevated levels of antioxidant enzymes including Cu/Zn‐superoxide dismutase (SOD1). Co‐transfection of Gβ 5 with RGS7 enhances SOD1 promoter activity and increases SOD1 protein expression in mammalian PC12 cells. Co‐transfection of Gβ 5 with Gγ or overexpression of other RGS proteins failed to activate the SOD1 promoter. Gβ 5 therefore acts with R7‐RGS proteins through an evolutionarily conserved pathway to lower ROS and protect neurons against oxidative stress. This research was supported in part by the Intramural Research Program of the NIH, NINDS (K‐T.M.) and NIDDK (W.F.S.) and by funds from the Ellison Medical Foundation (K‐T.M.).